Further Outpatient Care
See the list below:
-
Regular follow-up of the following parameters is necessary:
Growth and development should be monitored in children.
Chest radiograph and, if pulmonary abnormalities are suggested, high-resolution CT (HRCT) should be performed and repeated annually or as appropriate.
Pulmonary function tests should be performed and, if abnormal, monitored annually.
Immunoglobulin trough levels greater than or equal to 500 mg/dL are considered satisfactory, but levels greater than 600 mg/dL may be beneficial in patients with chronic lung or sinus disease. Doses and treatment intervals should be titrated in individual patients to determine the level needed to prevent recurrent infection without excessive use of this expensive medication.
Liver function tests should be performed and, if abnormalities are identified, nucleic acid tests should be used to determine if a potentially blood-borne infection (such as viral hepatitis) is present. Repeated results that suggest biliary disease may require follow-up with imaging studies of the liver and/or biliary tree to rule out malignancies or sclerosing cholangitis (the latter is seen in X-linked hyper-IgM syndrome [XHM]).
Lymphocyte surface marker analysis and serum immunoelectrophoresis may be indicated at routine intervals to screen for lymphoma and other malignancies.
Inpatient & Outpatient Medications
See the list below:
-
In most cases, intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) therapy can be given at home once safety has been established in the office/clinic. Home care nursing is usually required for IVIG therapy but may be unnecessary with SCIG.
-
Prophylactic and/or rotating full-treatment dose antibiotics may be useful in patients with chronic otitis, sinusitis, or chronic/recurrent bronchitis with bronchiectasis.
-
Bronchodilators, inhaled corticosteroids, inhaled anticholinergics, or a combination thereof may be indicated for patients whose lung disease includes components of bronchospasm, or bronchorrhea.
Transfer
See the list below:
-
Personnel at centers specializing in the diagnosis and treatment of these patients should be consulted for initial evaluation and treatment.
Deterrence/Prevention
See the list below:
-
Liberal use of antibiotics helps decrease the frequency of infections. Certain experts use a rotating regimen of antibiotics on a monthly basis.
Complications
See the list below:
-
Spruelike syndrome with malabsorption is observed in 10% of patients with common variable immunodeficiency (CVID). Upon small bowel biopsy, this syndrome resembles gluten-sensitive enteropathy, except for the absence of plasma cells. Infectious enteritis can be mistaken for ulcerative colitis or Crohn disease; both seem to occur with increased frequency in patients with CVID. Children with CVID frequently have lymphoid hyperplasia in the intestines, which may be comprised of plasmacytoid cells of B-cell lineage.
-
Vaccine-associated poliomyelitis may occur in patients with X-linked agammaglobulinemia (XLA) who receive the attenuated live poliovirus vaccine (no longer commonly used for infants in the United States).
-
Persistent enteroviral infection and chronic sinusitis remain the major complications of patients with XLA.
-
Viral encephalitis caused by, in decreasing order, enterovirus, coxsackievirus, measles, and papovavirus are potentially rare and devastating complications of hypogammaglobulinemia.
-
Hearing loss due to chronic otitis media or meningoencephalitis may affect as many as one third of patients with XLA and may also affect patients with CVID and specific antibody deficiency syndromes.
-
Bronchiectasis and cor pulmonale may complicate chronic or recurrent lower respiratory infections.
-
Autoimmune diseases [4]
The most common disorders are Coombs-positive hemolytic anemia and idiopathic thrombocytopenic purpura.
Neutropenia is observed less frequently. Nonimmune neutropenia is seen in young boys with XLA, and drug-induced neutropenia should be considered in other patients.
Pernicious anemia (due to autoimmunity) occurs in 10% of patients with CVID and is characterized by a younger age of onset and an absence of detectable antiparietal cell antibodies. Vitamin B12 deficiency should be considered in patients with CVID who do not have evidence of blood loss or iron deficiency.
Other less common autoimmune disorders have been reported, including thyroid diseases, Addison disease, diabetes mellitus, biliary cirrhosis, alopecia totalis, rheumatoid arthritis, systemic lupus erythematosus, polymyositis, sicca syndrome, and Guillain-Barré syndrome.
-
The risk of cancer in patients with CVID is 5 times higher than in matched controls. A 47-fold increase in gastric cancer and a 30-fold increase in lymphoma have been reported. The role of chronic infection with Helicobacter and other enteric pathogens in these cancers is suspected. Benign lymphoproliferative disorders are much more common, affecting up to 30% of patients, and manifest as splenomegaly, with or without diffuse lymphadenopathy. They are distinguished from lymphomas by the presence of a mixture of B and T lymphocytes and by the absence of clonal B-cell and T-cell receptor rearrangement.
-
A noncaseating granulomatous disease involving the lungs, lymph nodes, skin, bone marrow, and liver has been described in patients with CVID. [14] This entity should be differentiated from mycobacterial and fungal infections. In the small subset of patients with aggressive disease, corticosteroids and tumor necrosis factor (TNF) inhibitors are the treatments of choice. Granulomatous disease in the lungs is often associated with hilar, retroperitoneal, or abdominal lymphadenopathy.
-
Anaphylactic reactions can occur in rare instances when patients with IgA deficiency receive blood products containing IgA.
-
The risk of graft versus host disease (GVHD) is high in patients with SCID because of their inability to reject foreign antigens. Infants with SCID may present with GVHD before transplantation, due to engraftment with maternal lymphocytes before birth.
-
A dermatomyositis-like syndrome, a rare complication of Bruton disease, is a constellation of edema of subcutaneous tissue, rash, and muscle weakness. Chronic enteroviral meningoencephalitis also can be observed with this disorder.
-
Complications related to immunoglobulin therapy [20]
Nonanaphylactic reactions: The most common adverse reactions to IVIG are back and abdominal pain, nausea, vomiting, chills, fever, and myalgias. The infusion should be discontinued until the symptoms subside; then, it should be restarted at a slower rate after administration of premedication (eg, oral or intravenous hydration, antipyretics, antiemetics)
Local reactions to SCIG are common but are rarely persistent or serious.
Anaphylactic reactions: These are rare. They are IgE-mediated in patients with IgA deficiency and occur from seconds to hours after the infusion is started. IgG anti-IgA antibodies may be responsible for anaphylactoid reactions due to complement activation. Typical symptoms consist of flushing, facial swelling, dyspnea, and hypotension. The infusion should be stopped, and the patient should receive epinephrine, glucocorticoids, and antihistamines. Pure cutaneous reactions such as flushing and urticaria can be treated as nonanaphylactic reactions, with supportive and symptomatic therapy as needed.
Prognosis
See the list below:
-
Prognosis has improved significantly since the introduction of IVIG therapy to routine practice.
Mortality due to overwhelming infections remains a major risk for these patients, although chronic progressive morbidity is more likely.
Chronic lung and liver diseases result in significant morbidity and mortality.
The risk of malignancy, especially lymphomas involving mucosal-associated lymphoid tissue, must be kept in mind.
For those who survive long enough, autoimmune diseases and cancers become a serious threat because the incidence of these diseases is several-fold higher in these patients than in matched controls. [4]
SCID is a true pediatric emergency that may not be apparent on the newborn physical examination. [1] Patients do not survive beyond childhood unless a definitive treatment is performed. However, if hematopoietic stem cell transplantation is performed a bone within the first 3 months of life, the chance of survival is approximately 93%.
Patient Education
See the list below:
-
Despite aggressive IVIG therapy, these patients still have a higher incidence of infections compared to the general population.
-
Patients should be educated about the first symptoms of infection and the risk of overwhelming infections if they do not seek immediate medical attention.
-
Oral antibiotics covering encapsulated bacteria (eg, amoxicillin with or without clavulanic acid) should be made available for these patients at home for immediate use should they start experiencing symptoms of infection.
Tables
IVIG |
SCIG |
Advantages |
|
Dosing — large dose Intermittent and infrequent intervals High levels of IgG |
No venous access Self infusion Small volume Steady state levels of IgG — less "wear-off’ effects Compatible with working lifestyle Home treatment — convenient Less expensive Rare IgA reactions |
Disadvantages |
|
Needs venous access Trained personnel and healthcare facilities for administration Large fluctuations — "wear-off" effects More adverse effects May not suit a busy working lifestyle |
More frequent dosing and injections Smaller volume/dose and multiple infusion sites Needs education Nonadherence issues likely |
